{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:18:12Z","timestamp":1790788692819,"version":"4.1.0"},"reference-count":12,"publisher":"National Academy of Sciences","issue":"1","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,1,5]]},"abstract":"\n We identified an autosomal recessive condition in 11 individuals in the Old Order Amish of northeastern Ohio. The syndrome was characterized by distinctive craniofacial dysmorphism, skeletal anomalies, and mental retardation. The typical craniofacial dysmorphism included brachycephaly, highly arched bushy eyebrows, synophrys, long eyelashes, low-set ears, microdontism of primary teeth, and generalized gingival hyperplasia, whereas Sprengel deformity of scapula, fusion of spine, rib abnormities, pectus excavatum, and pes planus represented skeletal anomalies. The genome-wide homozygosity mapping using six affected individuals localized the disease gene to a 3.3-Mb region on chromosome 1q23.3-q24.1. Candidate gene sequencing identified a homozygous frameshift mutation, c.139_140delAG, in the transmembrane and coiled-coil domains 1 (\n TMCO1)<\/jats:italic>\n gene, as the pathogenic change in all affected members of the extended pedigree. This mutation is predicted to result in a severely truncated protein (p.Ser47Ter) of only one-fourth the original length. The\n TMCO1<\/jats:italic>\n gene product is a member of DUF841 superfamily of several eukaryotic proteins with unknown function. The gene has highly conserved amino acid sequence and is universally expressed in all human tissues examined. The high degree of conservation and the ubiquitous expression pattern in human adult and fetal tissues suggest a critical role for\n TMCO1<\/jats:italic>\n . This report shows a\n TMCO1<\/jats:italic>\n sequence variant being associated with a genetic disorder in human. We propose \u201cTMCO1 defect syndrome\u201d as the name of this condition.\n <\/jats:p>","DOI":"10.1073\/pnas.0908457107","type":"journal-article","created":{"date-parts":[[2009,12,14]],"date-time":"2009-12-14T22:19:27Z","timestamp":1260829167000},"page":"258-263","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":63,"title":["Homozygous frameshift mutation in\n TMCO1<\/i>\n causes a syndrome with craniofacial dysmorphism, skeletal anomalies, and mental retardation"],"prefix":"10.1073","volume":"107","author":[{"given":"Baozhong","family":"Xin","sequence":"first","affiliation":[{"name":"DDC Clinic for Special Needs Children, Middlefield, OH 44062;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik G.","family":"Puffenberger","sequence":"additional","affiliation":[{"name":"The Clinic for Special Children, Strasburg, PA 17579;"},{"name":"Department of Biology, Franklin and Marshall College, Lancaster, PA 17603;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Turben","sequence":"additional","affiliation":[{"name":"DDC Clinic for Special Needs Children, Middlefield, OH 44062;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Cleveland State University, Cleveland, OH 44115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Cleveland State University, Cleveland, OH 44115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Wang","sequence":"additional","affiliation":[{"name":"DDC Clinic for Special Needs Children, Middlefield, OH 44062;"},{"name":"Department of Pediatrics, Rainbow Babies and Children\u2019s Hospital, Cleveland, OH 44106; and"},{"name":"Department of Molecular Cardiology, Cleveland Clinic, Cleveland, OH 44195"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,12,29]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddl189"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0401194101"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa052773"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31981"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2008.01018.x"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genom-082908-150040"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.09.026"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0507066103"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2008.07.007"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0805139105"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a022435"},{"key":"e_1_3_3_12_2","article-title":"Molecular cloning, expression patterns and subcellular localization of porcine TMCO1 gene","author":"Zhang Z","year":"2009","unstructured":"Z Zhang, et al., Molecular cloning, expression patterns and subcellular localization of porcine TMCO1 gene. Mol Biol Rep, in press. (2009).","journal-title":"Mol Biol Rep"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0908457107","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T19:12:06Z","timestamp":1649790726000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0908457107"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,12,29]]},"references-count":12,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2010,1,5]]}},"alternative-id":["10.1073\/pnas.0908457107"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0908457107","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,12,29]]},"assertion":[{"value":"2009-12-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}